The kidneys excrete waste and contribute to maintenance of homeostasis by regulating blood pH, electrolyte levels and blood pressure. Renal failure or dysfunction is the cause of several diseases whose clinical manifestations are typically hyper- or hypo-tension. These diseases include Bartter's syndrome, Gitelman syndrome, autosomal dominant polycystic kidney disease, and nephrolithiasis.
Treatment with antibiotics such as gentamicin, tobramycin, or amikacin can lead to tubular necrosis with consequent risk of acute renal failure in as much as 25% of patients. A cumulative dose of 2 to 3 grams amphotericin B is likewise nephrotoxic. Cyclosporine, an immunosuppressant given to organ transplant patients, is also nephrotoxic. The molecular basis for the nephrotoxicity of these and other compounds is not understood, although calbindin D levels appear to be a useful diagnostic marker signaling cyclosporine-induced nephrotoxicity (Aicher et al. (1998) Electrophoresis 19:1998-2003). Similarly, reductions in urinary excretion of proteins such as Tamm-Horsfall protein, beta 2 microglobin, and urinary retinol binding protein, appear to be diagnostic for nephrctoxicity when induced by certain chemotherapeutic agents including ifosfamide and cisplatinum (MacLean et al. (1998) Cancer Chemother. Pharmacol. 41:413-6; Tokuc et al. (1997) J. Exp. Clin. Cancer Res. 16:227-30).
We have identified nine novel kidney disease-associated genes through their co-expression with genes known to affect kidney function in normal and diseased states. The present invention satisfies a need in the art by providing new amino acid and nucleic acid compositions that are useful for diagnosis, prognosis, treatment, prevention, and evaluation of therapies for renal disorders.